Somatostatin
is
a
peptide
hormone
that
regulates
endocrine
systems
by
binding
to
G-protein-coupled
somatostatin
receptors.
receptor
2
(SSTR2)
human
and
highly
implicated
in
disorders,
cancers,
neurological
diseases.
Here,
we
report
the
high-resolution
cryo-EM
structure
of
full-length
SSTR2
bound
agonist
(SST-14)
complex
with
inhibitory
G
(G
i
)
proteins.
Our
structural
mutagenesis
analyses
show
seven
transmembrane
helices
form
deep
pocket
for
ligand
recognizes
conserved
Trp-Lys
motif
SST-14
at
bottom
pocket.
Furthermore,
our
sequence
analysis
combined
AlphaFold
modeled
structures
other
SSTR
isoforms
provide
basis
mechanism
which
family
proteins
specifically
interact
their
cognate
ligands.
This
work
provides
first
glimpse
into
molecular
recognition
receptors
crucial
resource
develop
therapeutics
targeting
Frontiers in Neurology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 7, 2025
White
matter
hyperintensities
(WMHs)
are
commonly
detected
on
T2-weighted
magnetic
resonance
imaging
(MRI)
scans,
occurring
in
both
typical
aging
and
Alzheimer's
disease
(AD).
Despite
their
frequent
appearance
association
with
cognitive
decline
AD,
the
molecular
factors
contributing
to
WMHs
remain
unclear.
In
this
study,
we
investigated
transcriptomic
profiles
of
two
affected
brain
regions
coincident
AD
pathology-frontal
subcortical
white
(frontal-WM)
occipital
(occipital-WM)-and
compared
age-matched
cognitively
intact
controls.
Through
RNA-sequencing
frontal-
occipital-WM
bulk
tissues,
identified
an
upregulation
genes
associated
vasculature
function
matter.
To
further
elucidate
vasculature-specific
features,
performed
RNA-seq
analysis
blood
vessels
isolated
from
these
regions,
which
revealed
related
protein
folding
pathways.
Finally,
comparing
gene
expression
between
individuals
high-
versus
low-WMH
burden
showed
increased
pathways
immune
function.
Taken
together,
our
study
characterizes
diverse
changes
provides
mechanistic
insights
into
processes
underlying
AD-related
WMHs.
Egyptian Journal of Medical Human Genetics,
Journal Year:
2025,
Volume and Issue:
26(1)
Published: Jan. 20, 2025
Abstract
Background
Parkinson’s
disease
(PD)
is
a
neurodegenerative
condition
marked
by
the
gradual
degeneration
of
dopaminergic
neurons
in
substantia
nigra,
leading
to
depletion
nigra
as
well
and
decreased
activity
putamen.
This
study
aims
identify
role
putamen
non-motor
PD
symptoms
potential
therapeutic
target
PD.
Methods
Transcriptome
profiles
(dataset
number:
GSE205450,
obtained
from
postmortem
caudate
samples
forty
controls
thirty-five
patients)
were
retrieved
Gene
Expression
Omnibus
(GEO)
database.
Specifically,
we
focused
on
data
for
patients.
Differential
gene
expression
analysis
was
carried
out
using
with
Limma,
filtering
genes
|logFC|>
1
(fold
change)
p
<
0.05
(
-value).
Protein–Protein
Interaction
networks
constructed
stringDB
(combined
score
>
0.7)
analyzed
Cytoscape
hub
based
various
topological
measures
(EPC,
MCC,
MNC,
Degree,
EcCentricity).
Enrichment
conducted
Ontology
(GO)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG).
Also,
transcription
factor
(TF)-hub
networks,
miRNA-hub
association
JASPAR
database,
Tarbase
DisGeNET
via
NetworkAnalyst
platform,
respectively.
Results
Seven
genes,
namely
SST
,
NPY
IL6
PVALB
ALB
NTS
TH
identified
Notable
miRNAs
included
hsa-mir-34a-5p,
hsa-mir-15a-5p,
hsa-mir-424-5p,
hsa-mir-19b-3p
while
key
factors
include
GATA2,
CREB1,
FOXC1,
FOXL1,
TID1,
NFKB1,
YY1,
SPIB,
GATA3,
STAT3
.
Conclusions
Our
findings
revealed
close
associations
between
such
major
depressive
disorder,
mood
disorders
schizophrenia.
These
may
provide
new
direction
developing
therapy
wet
lab
research
encouraged.
The
dorsal
vagal
complex
(DVC)
is
a
region
in
the
brainstem
comprised
of
an
intricate
network
specialized
cells
responsible
for
sensing
and
propagating
many
appetite-related
cues.
Understanding
dynamics
controlling
appetite
requires
deeply
exploring
cell
types
transitory
states
harbored
this
brain
site.
We
generated
multi-species
DVC
atlas
using
single
nuclei
RNAseq
(sn-RNAseq),
by
curating
harmonizing
mouse
rat
data,
which
includes
>180,000
123
identities
at
5
granularities
cellular
resolution.
report
unique
features
such
as
Kcnj3
expression
Ca
+
-permeable
astrocytes
well
new
populations
like
neurons
co-expressing
Th
Cck
,
leptin
receptor-expressing
neuron
population
area
postrema
marked
progenitor
marker,
Pdgfra
.
In
summary,
our
findings
demonstrate
high
degree
complexity
within
provide
valuable
tool
study
metabolic
center.
The
dorsal
vagal
complex
(DVC)
is
a
region
in
the
brainstem
comprised
of
an
intricate
network
specialized
cells
responsible
for
sensing
and
propagating
many
appetite-related
cues.
Understanding
dynamics
controlling
appetite
requires
deeply
exploring
cell
types
transitory
states
harbored
this
brain
site.
We
generated
multi-species
DVC
atlas
using
single
nuclei
RNAseq
(sn-RNAseq),
by
curating
harmonizing
mouse
rat
data,
which
includes
>180,000
123
identities
at
5
granularities
cellular
resolution.
report
unique
features
such
as
Kcnj3
expression
Ca
+
-permeable
astrocytes
well
new
populations
like
neurons
co-expressing
Th
Cck
,
leptin
receptor-expressing
neuron
population
area
postrema
marked
progenitor
marker,
Pdgfra
.
In
summary,
our
findings
demonstrate
high
degree
complexity
within
provide
valuable
tool
study
metabolic
center.
Somatostatin
is
a
peptide
hormone
that
regulates
endocrine
systems
by
binding
to
G-protein-coupled
somatostatin
receptors.
receptor
2
(SSTR2)
human
and
highly
implicated
in
disorders,
cancers,
neurological
diseases.
Here,
we
report
the
high-resolution
cryo-EM
structure
of
full-length
SSTR2
bound
agonist
(SST-14)
complex
with
inhibitory
G
(G
i
)
proteins.
Our
structural
mutagenesis
analyses
show
seven
transmembrane
helices
form
deep
pocket
for
ligand
recognizes
conserved
Trp-Lys
motif
SST-14
at
bottom
pocket.
Furthermore,
our
sequence
analysis
combined
AlphaFold
modeled
structures
other
SSTR
isoforms
provide
basis
mechanism
which
family
proteins
specifically
interact
their
cognate
ligands.
This
work
provides
first
glimpse
into
molecular
recognition
receptors
crucial
resource
develop
therapeutics
targeting
